title: Obesity and sleep disturbances: meaningful sub-typing of obesity.
abstract: Obesity, excessive daytime sleepiness (EDS), and self-reported short sleep duration appear to be on the rise, while there is evidence that obesity and these sleep disorders are strongly connected. In this paper, we review data that challenge the common belief that the sleep apnoea and sleep loss, frequently associated with obesity, are the primary determinants of obesity-related objective daytime sleepiness and subjective fatigue (tiredness without increased sleep propensity). Specifically, obesity is associated with objective and subjective EDS regardless of the presence of sleep apnoea. The association between obesity and EDS was confirmed in recent studies of large random samples of the general population or clinical samples, which showed that the primary determinants of subjective EDS were depression, metabolic disturbances, i.e. obesity/diabetes and insulin resistance, and lack of physical activity, and, secondarily, sleep apnoea or sleep loss. Paradoxically, within the obese, with or without sleep apnoea, those who slept objectively better at night are sleepier (objectively) during the day than those who slept worse. The distinguishing factor between those that slept better vs. those that slept worse appears to be level of emotional stress. Furthermore, many studies reported that obesity is associated with self-reported short sleep duration; however, it appears that short sleep duration is a marker of emotional stress rather than a reflection of true sleep loss. Based on these data, we propose that obesity-related deeper sleep and objective EDS are primarily related to metabolic disturbances, whereas obesity-related poorer sleep and subjective fatigue appear to be the result of psychological distress. Furthermore, based on data from studies in normal controls and patients with sleep disorders, it appears that the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines determines the level of sleep/arousal within the 24-hour cycle, i.e. "eucortisolemia" or "hypocortisolemia" plus hypercytokinemia is associated with high sleep efficiency and objective sleepiness, whereas "hypercortisolemia" plus hypercytokinemia is associated with low sleep efficiency and fatigue. In conclusion, we propose that the above-reviewed data provide the basis for a meaningful phenotypic and pathophysiologic sub-typing of obesity. One subtype is associated with emotional distress, poor sleep, fatigue, HPA axis "hyperactivity," and hypercytokinemia while the other is associated with non-distress, better sleep but more sleepiness, HPA axis "normo or hypoactivity," and hypercytokinemia. This proposed sub-typing may lead to novel, preventive and therapeutic strategies for obesity and its associated sleep disturbances.
authors.affiliation: Sleep Research and Treatment Center, Department of Psychiatry, Penn State College of Medicine, Hershey, PA 17033, USA. avgontzas@psu.edu
authors.forename: Alexandros N
authors.initials: AN
authors.lastname: Vgontzas
authors.forename: Edward O
authors.initials: EO
authors.lastname: Bixler
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Pejovic
mesh_terms: D000342:Affective Symptoms / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008954:Models, Biological; D009765:Obesity / Q000145:classification* / Q000150:complications / Q000175:diagnosis*; D012044:Regression Analysis; D012307:Risk Factors; D012890:Sleep; D012893:Sleep Wake Disorders / Q000150:complications* / Q000175:diagnosis*
chemical_list: D016207:Cytokines